Elevations in plasma cortisol levels have been reported in certain types of affective depression. Furthermore, adrenal hyper and hypo-function can produce pronounced mood alterations. The possible role of glucocorticoid in the psychopathology of affective disorders, however, has not been established. Preliminary work with cat spinal reflex pathways as model systems has disclosed that intensive glucocorticoid dosing enhances neuronal terminal excitability and reflex transmission and alters bulbospinal monoaminergic regulation of monosynaptic transmission. Studies are proposed herein to further define the acute vs. chronic effects of glucocorticoids on spinal excitatory vs. inhibitory synaptic function and biogenic amine modulation of reflex excitability. The ability of acute glucocorticoid administration to modify tricyclic antidepressant-monoamine interactions in relation to spinal activity will be extended. Intracellular recording techniques will be used to investigate glucocorticoid effects on motor neuron membrane electrical properties. Pharmacokinetic measurement of glucocorticoid levels in plasma and spinal cord tissue after acute administration will be done to provide a correlate for electrophysiological actions. Neurochemical experiments will be conducted to assess steroid actions on both the steady-state cord levels of norepi, dopamine and 5-OH tryptamine and using radioactive precursers, their turnover rates. In addition, the effects of adrenalectomy and acute glucocorticoid replacement therapy on excitatory an inhibitory reflex transmission, monoaminergic reflex modulation, antidepressant drug action on reflexes, motor neuron electrical properties and biogenic amine turnover will be throughly studied. This research may uncover a relationship between endogenous glucocorticoids, biogenic amines and the symptomatology of affective illness.